Based on our findings in this work

Based on our findings in this work as well as the previous published data in the experimental mice model of RSV infection, we suggest that modulation of 12/15 LOX expression and/or blocking of LOX products such as 12(S)-HETE may represent potential pharmacological approaches to prevent or treat viral-induced lung inflammation and its long-term consequences [23]. Other possible mechanisms of the interaction between 12/15-LOX pathway and RSV pathogenesis also require discussion. Production of reactive oxygen species (ROS) during RSV infection is one the important ways that neutrophils can injure the lungs [2], [24], [25]. Lipoxygenases are considered as an important source of producing ROS inside the DIDS synthesis [26]. Several studies have indicated that the 12/15-LOX is a pro-inflammatory pathway and mediates an elevation in inflammation and oxidative stress in different tissues [27]. Therefore LOX inhibitors have a protective effect in inflammatory diseases because of their anti-inflammatory activity [26]. Based on pervious strong supportive evidences indicating that RSV-induced intracellular ROS formation [23] and our results revealing the expression of pro-inflammatory mediators and 12/15 LOX, it can be accounts as an important pathogenetic mechanism of RSV-induced lung disease, and anti-LOX products intervention may represent a rational approach for treatment of RSV [15]. Adhesion molecules also are involved in the pathophysiology of RSV-associated diseases [28]. In RSV infection, ICAM-1, VCAM-1, and E-selectin are involved in neutrophil interactions with the endothelium [28], [29]. Neutrophils are the predominant airway leukocytes invading the airways in RSV bronchiolitis [2], [29]. It was shown that 15(S)-HETE up-regulated the expression of E-selectin in the endothelial cells [30]. A threefold increase in the level of E-selectin in cultures treated with 15(S)-HETE compared to control was reported. One possible mechanism is the involvement of LOX pathway in the adhesion molecules expression such as ICAM-1, VCAM-1, and E-selectin and make an important role in leukocytes infiltration and RSV bronchiolitis.
Disclosure
Acknowledgments We thank the following people for their contributions to this work: Maryam Golara, Fatemeh Adjaminejad and Azadeh Shadab for the technical support. This research was supported by School of Public Health, Tehran University of Medical Sciences [92-01-27-21977].
Value of the data
Data Here we present immunohistochemical and qPCR data showing that lipoxygenases-5 and -12 are also activated during acetaminophen-induced liver damage[1]. The lipoxygenase-5 appeared to be weakly expressed in the normal liver parenchyma (Fig. 1A, 40× magnification), but at 48h acetaminophen administration consistently enhanced its expression in the damaged livers[2], primarily around the centrilobular veins (Fig. 1B, 40× magnification). The lipoxygenase-12 also appeared to stain weakly the normal liver parenchyma (Fig. 1C, 40× magnification), whereas acetaminophen administration enhanced, but only modestly, its expression at 48h (Fig. 1D, 40× magnification), especially around the centrilobular veins[3]. The expression pattern of lipoxygenase-12 overlapped with that observed for the lipoxygenase-5 in the damaged liver. When the expression of lipoxygenase-5 and -12 was examined in the control and acetaminophen-treated livers, we found that at 48h, the expression of both lipoxygenases was up-regulated, but significant differences were found only for lipoxygenase-5 (Fig. 1E and F).
Experimental design, materials and methods
Statistical analysis The data are displayed as mean (X)±SE from at least three independent experiments. Statistical analysis was performed with the statistical package Gnumeric Spreadsheet (Gnome Foundation, Orinda, CA, USA). Planned pairwise comparisons between groups were performed by using Student׳s t-tests; p<0.05 was the criterion of significance.